Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase.

ABSTRACT: A major factor contributing to the high mutation rate of HIV-1 reverse transcriptase (RT) is its high propensity for misincorporation. Misincorporation requires both deoxyribonucleotide triphosphate (dNTP) misinsertion and the subsequent extension of the mismatched terminus thus formed. We hypothesized that Lys66 is a determinant of mismatch extension based on its position near the primer terminus. This hypothesis was tested by steady-state kinetic studies using wild-type HIV-1 RT and four Lys66 substitution mutants: Lys66Arg, Lys66Ala, Lys66Asn and Lys66Thr. The mismatch extension efficiency was reduced for all mutants, with Lys66Ala, Lys66Asn and Lys66Thr showing a four- to six-fold reduction compared with wild-type HIV-1 RT. Surprisingly, the nonconservative substitutions also led to la

SUBMITTER: Lwatula C 

PROVIDER: S-EPMC3472125 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature